Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.

S-(2-Succinyl)cysteine:a novel chemical modification of tissue proteins by a Krebs cycle intermediate

S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

Adaptive Measurement-Based Policy-Driven QoS Management with Fuzzy-Rule-based Resource Allocation

Fixed and wireless networks are increasingly converging towards common connectivity with IP-based core networks. Providing effective end-to-end resource and QoS management in such complex heterogeneous converged network scenarios requires unified, adaptive and scalable solutions to integrate and co-ordinate diverse QoS mechanisms of different access technologies with IP-based QoS. Policy-Based Network Management (PBNM) is one approach that could be employed to address this challenge. Hence, a policy-based framework for end-to-end QoS management in converged networks, CNQF (Converged Networks QoS Management Framework) has been proposed within our project. In this paper, the CNQF architecture, a Java implementation of its prototype and experimental validation of key elements are discussed. We then present a fuzzy-based CNQF resource management approach and study the performance of our implementation with real traffic flows on an experimental testbed. The results demonstrate the efficacy of our resource-adaptive approach for practical PBNM systems

Implementation and Evaluation of Measurement-Based Admission Control Schemes Within a Converged Networks QoS Management Framework

Policy-based network management (PBNM) paradigms provide an effective tool for end-to-end resource
management in converged next generation networks by enabling unified, adaptive and scalable solutions
that integrate and co-ordinate diverse resource management mechanisms associated with heterogeneous
access technologies. In our project, a PBNM framework for end-to-end QoS management in converged
networks is being developed. The framework consists of distributed functional entities managed within a
policy-based infrastructure to provide QoS and resource management in converged networks. Within any
QoS control framework, an effective admission control scheme is essential for maintaining the QoS of
flows present in the network. Measurement based admission control (MBAC) and parameter basedadmission control (PBAC) are two commonly used approaches. This paper presents the implementationand analysis of various measurement-based admission control schemes developed within a Java-based
prototype of our policy-based framework. The evaluation is made with real traffic flows on a Linux-based experimental testbed where the current prototype is deployed. Our results show that unlike with classic MBAC or PBAC only schemes, a hybrid approach that combines both methods can simultaneously result in improved admission control and network utilization efficiency

Dynamic Buffer Management for Multimedia Services in Beyond 3G Wireless Networks

This paper investigates a dynamic buffer man-agement scheme for QoS control of multimedia services in be-yond 3G wireless systems. The scheme is studied in the context of the state-of-the-art 3.5G system i.e. the High Speed Downlink Packet Access (HSDPA) which enhances 3G UMTS to support high-speed packet switched services. Unlike earlier systems, UMTS-evolved systems from HSDPA and beyond incorporate mechanisms such as packet scheduling and HARQ in the base station necessitating data buffering at the air interface. This introduces a potential bottleneck to end-to-end communication. Hence, buffer management at the air interface is crucial for end-to-end QoS support of multimedia services with multi-plexed parallel diverse flows such as video and data in the same end-user session. The dynamic buffer management scheme for HSDPA multimedia sessions with aggregated real-time and non real-time flows is investigated via extensive HSDPA simulations. The impact of the scheme on end-to-end traffic performance is evaluated with an example multimedia session comprising a real-time streaming flow concurrent with TCP-based non real-time flow. Results demonstrate that the scheme can guar-antee the end-to-end QoS of the real-time streaming flow, whilst simultaneously protecting the non real-time flow from starva-tion resulting in improved end-to-end throughput performance

Measurement-based Policy-driven QoS Management in Converged Next Generation Networks

Policy-based management is considered an effective approach to address the challenges of resource management in large complex networks. Within the IU-ATC QoS Frameworks project, a policy-based network management framework, CNQF (Converged Networks QoS Framework) is being developed aimed at providing context-aware, end-to-end QoS control and resource management in converged next generation networks. CNQF is designed to provide homogeneous, transparent QoS control over heterogeneous access technologies by means of distributed functional entities that co-ordinate the resources of the transport network through policy-driven decisions. In this paper, we present a measurement-based evaluation of policy-driven QoS management based on CNQF architecture, with real traffic flows on an experimental testbed. A Java based implementation of the CNQF Resource Management Subsystem is deployed on the testbed and results of the experiments validate the framework operation for policy-based QoS management of real traffic flows.

Dynamic Buffer Management for Multimedia Services in 3.5G Wireless Networks

This paper presents and investigates a dynamic
buffer management scheme for QoS control of multimedia
services in a 3.5G wireless system i.e. the High Speed Downlink
Packet Access (HSDPA). HSDPA was introduced to enhance
UMTS for high-speed packet switched services. With HSDPA,
packet scheduling and HARQ mechanisms in the base station
require data buffering at the air interface thus introducing a
potential bottleneck to end-to-end communication. Hence, for
multimedia services with multiplexed parallel diverse flows
such as video and data in the same end-user session, buffer
management schemes in the base station are essential to support
end-to-end QoS provision. We propose a dynamic buffer management
scheme for HSDPA multimedia sessions with aggregated real-time and non real-time flows in the paper. The end-to-end performance impact of the scheme is evaluated with an example multimedia session comprising a real-time streaming
flow concurrent with TCP-based non real-time flow via extensive HSDPA simulations. Results demonstrate that the scheme can guarantee the end-to-end QoS of the real-time streaming flow, whilst simultaneously protecting non real-time flow from starvation resulting in improved end-to-end throughput performance

Automated Methods for Virtual Maintainability & Aerospace Maintenance Planning

Abstract. Modern business practices in engineering are increasingly turning to post manufacture service provision in an attempt to generate additional revenue streams and ensure commercial sustainability. Maintainability has always been a consideration during the design process but in the past it has been generally considered to be of tertiary importance behind manufacturability and primary product function in terms of design priorities. The need to draw whole life considerations into concurrent engineering (CE) practice has encouraged companies to address issues such as maintenance, earlier in the design process giving equal importance to all aspects of the product lifecycle. The consideration of design for maintainability (DFM) early in the design process has the potential to significantly reduce maintenance costs, and improve overall running efficiencies as well as safety levels. However a lack of simulation tools still hinders the adaptation of CE to include practical elements of design and therefore further research is required to develop methods by which ‘hands on’ activities such as maintenance can be fully assessed and optimised as concepts develop. Virtual Reality (VR) has the potential to address this issue but the application of these traditionally high cost systems can require complex infrastructure and their use has typically focused on aesthetic aspects of mature designs. This paper examines the application of cost effective VR technology to the rapid assessment of aircraft interior inspection during conceptual design. It focuses on the integration of VR hardware with a typical desktop engineering system and examines the challenges with data transfer, graphics quality and the development of practical user functions within the VR environment. Conclusions drawn to date indicate that the system has the potential to improve maintenance planning through the provision of a usable environment for inspection which is available as soon as preliminary structural models are generated as part of the conceptual design process. Challenges still exist in the efficient transfer of data between the CAD and VR environments as well as the quantification of any benefits that result from the proposed approach. The result of this research will help to improve product maintainability, reduce product development cycle times and lower maintenance costs.

Ergodic Capacity of Cognitive TAS/GSC Relaying in Nakagami-m Fading Channels

We examine the impact of transmit antenna selection with receive generalized selection combining (TAS/GSC) for cognitive decode-and-forward (DF) relaying in Nakagami-m fading channels. We select a single transmit antenna at the secondary transmitter which maximizes the receive signal-to-noise ratio (SNR) and combine a subset of receive antennas with the largest SNRs at the secondary receiver. In an effort to assess the performance, we first derive the probability density function and cumulative distribution function of the end-to-end SNR using the moment generating function. We then derive new exact closed-form expression for the ergodic capacity. More importantly, by deriving the asymptotic expression for the high SNR approximation of the ergodic capacity, we gather deep insights into the high SNR slope and the power offset. Our results show that the high SNR slope is 1/2 under the proportional interference power constraint. Under the fixed interference power constraint, the high SNR slope is zero.

A new look at dual-hop relaying: Performance limits with hardware impairments

Physical transceivers have hardware impairments that create distortions which degrade the performance of communication systems. The vast majority of technical contributions in the area of relaying neglect hardware impairments and, thus, assume ideal hardware. Such approximations make sense in low-rate systems, but can lead to very misleading results when analyzing future high-rate systems. This paper quantifies the impact of hardware impairments on dual-hop relaying, for both amplify-and-forward and decode-and-forward protocols. The outage probability (OP) in these practical scenarios is a function of the effective end-to-end signal-to-noise-and-distortion ratio (SNDR). This paper derives new closed-form expressions for the exact and asymptotic OPs, accounting for hardware impairments at the source, relay, and destination. A similar analysis for the ergodic capacity is also pursued, resulting in new upper bounds. We assume that both hops are subject to independent but non-identically distributed Nakagami-m fading. This paper validates that the performance loss is small at low rates, but otherwise can be very substantial. In particular, it is proved that for high signal-to-noise ratio (SNR), the end-to-end SNDR converges to a deterministic constant, coined the SNDR ceiling, which is inversely proportional to the level of impairments. This stands in contrast to the ideal hardware case in which the end-to-end SNDR grows without bound in the high-SNR regime. Finally, we provide fundamental design guidelines for selecting hardware that satisfies the requirements of a practical relaying system.

Maintaining design intent for aircraft manufacture

Design and manufacture of aircraft requires deep multi-disciplinary understanding of system behaviour. The intention of the designer can get lost due to the many changes occurring to the product and the inability of the methods and tools used to capture it. Systems engineering and optimisation tools underpin industrial approaches to design, but are not without issue. The challenge is to find a route from concept to manufacture which enables designers to maintain their original intent. The novelty in this work is that the parameterisation used to build the CAD model reflects the manufacturing capability, ensuring design intent is maintained from concept to manufacture.

Performance Analysis of Randomized Distributed Space-Time Codes over Composite Gamma/Lognormal Fading Channels

This work investigates the end-to-end performance of randomized distributed space-time codes with complex Gaussian distribution, when employed in a wireless relay network. The relaying nodes are assumed to adopt a decode-and-forward strategy and transmissions are affected by small and large scale fading phenomena. Extremely tight, analytical approximations of the end-to-end symbol error probability and of the end-to-end outage probability are derived and successfully validated through Monte-Carlo simulation. For the high signal-to-noise ratio regime, a simple, closed-form expression for the symbol error probability is further provided.

Realizing Accelerated Cost-Effective Distributed RAID

The exponential growth in user and application data entails new means for providing fault tolerance and protection against data loss. High Performance Com- puting (HPC) storage systems, which are at the forefront of handling the data del- uge, typically employ hardware RAID at the backend. However, such solutions are costly, do not ensure end-to-end data integrity, and can become a bottleneck during data reconstruction. In this paper, we design an innovative solution to achieve a flex- ible, fault-tolerant, and high-performance RAID-6 solution for a parallel file system (PFS). Our system utilizes low-cost, strategically placed GPUs — both on the client and server sides — to accelerate parity computation. In contrast to hardware-based approaches, we provide full control over the size, length and location of a RAID array on a per file basis, end-to-end data integrity checking, and parallelization of RAID array reconstruction. We have deployed our system in conjunction with the widely-used Lustre PFS, and show that our approach is feasible and imposes ac- ceptable overhead.

Relational architecture description language for software families

Software Product-Line Engineering has emerged in recent years, as an important strategy for maximising reuse within the context of a family of related products. In current approaches to software product-lines, there is general agreement that the definition of a reference-architecture for the product-line is an important step in the software engineering process. In this paper we introduce ADLARS, a new form of architecture Description language that places emphasis on the capture of architectural relationships. ADLARS is designed for use within a product-line engineering process. The language supports both the definition of architectural structure, and of important architectural relationships. In particular it supports capture of the relationships between product features, component and task architectures, interfaces and parameter requirements.

Thermal properties and eutectic behaviour of dapivirine in combination with steroid hormones and other antiretrovirals

Background: Combination drug products can display thermal behaviour that is more complex than for the corresponding single drug products. For example, the contraceptive vaginal ring (VR) Nuvaring contains a eutectic (lowest melting) composition of etonogestrel (ETN) and ethinyl estradiol. Here we report the predisposition of dapivirine (DPV) to form reduced melting/eutectic mixtures when combined with other contraceptive hormones and antiretrovirals, and discuss the implications for development of combination microbicide and multipurpose prevention technology (MPT) products.
Methods: Binary mixtures of DPV with darunavir (DRV), levonorgestrel (LNG), ETN or maraviroc (MVC) were prepared either by physical mixing or by solvent evaporation. Selected binary mixtures were also incorporated into silicone elastomer (SE) VR devices. Thermal behavior of the mixtures was analyzed using differential scanning calorimetry (DSC) operating in standard heating ramp mode (10 °C/min). DSC data were used to construct two component phase diagrams for each binary system.
Results: Drug mixtures typically showed reduced melting transitions for both drug components, with clear evidence for a eutectic mixture at a well-defined intermediate composition. Eutectic temperatures and compositions for the various mixtures were: 40% DPV / 60% ETN - 170°C; 25% DPV / 75% MVC - 172°C; 65% DPV / 35% LNG - 192°C. In each case, the eutectic composition was also detected when the drug mixtures were incorporated into SE VRs. For the DPV/DRV system, the thermal behaviour is complicated by desolvation from the darunavir ethanolate polymorph.
Conclusions: When DPV is combined with small molecular weight hydrophobic drugs, the melting temperature for both drugs is typically reduced to a degree dependent on the composition of the mixture. At specified compositions, a low melting eutectic system results. The formation of eutectic behavior in binary drug systems needs to be carefully characterised in order to define product performance and drug release.